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Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer

ConditionsFallopian Tube Endometrioid AdenocarcinomaFallopian Tube High Grade Serous AdenocarcinomaFallopian Tube Malignant Mixed Mesodermal (Mullerian) TumorFIGO Stage III Ovarian Cancer 2014FIGO Stage IV Ovarian Cancer 2014Ovarian CarcinomaOvarian CarcinosarcomaOvarian High Grade Endometrioid AdenocarcinomaOvarian High Grade Serous AdenocarcinomaPrimary Peritoneal CarcinosarcomaPrimary Peritoneal Endometrioid AdenocarcinomaPrimary Peritoneal High Grade Serous Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorNRG Oncology

About this trial

This phase III trial compares the effect of olaparib for one year versus two years, with or without bevacizumab, for the treatment of BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer. Olaparib is a polyadenosine 5'-diphosphoribose polymerase (PARP) enzyme inhibitor and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving olaparib for one year with or without bevacizumab may be effective in treating patients with BRCA 1/2 mutated or homologous recombination deficient stage III or IV ovarian cancer, when compared to two years of olaparib.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

High grade serous

High grade endometrioid (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated)

Carcinosarcoma (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated), and/or

Other epithelial ovarian cancer with BRCA1/2 deleterious alteration (germline or somatic), (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated)

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bevacizumab

    Biological/Vaccine

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Olaparib

    Drug

    Given PO

Treatment groups

880 Participants
are divided into 2 treatment groups
Group A: Arm I (olaparib, bevacizumab)Active comparator 5 interventions
Group B: Arm II (olaparib, bevacizumab)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS) at least 360 days after randomization (PFS360)

PFS will be tested using a one-sided, alpha = 0.05 level logrank test. Treatment hazard ratios and their 90% confidence intervals will be estimated using a Cox proportional hazards model specified with a main effect for the randomized treatment assignment and stratified using the stratification factors applied at randomization.

Time frame
From completing 360 days of maintenance therapy to disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) or death, whichever occurs first, assessed up to 5 years

Secondary outcomes

1

Overall survival (OS) 360

This endpoint will be supported by the modified intent to treat (ITT) population, which excludes progressions, deaths or withdrawals within 359 days of randomization. Will be summarized using treatment hazard ratio estimates (90% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. OS distributions will be summarized using methods developed by Kaplan-Meier.

Time frame
From 360 days after randomization to death from any cause, assessed up to 5 years
2

PFS

Will be analyzed in the ITT population and serve as a sensitivity analysis for the primary endpoint. Will be summarized using treatment hazard ratio estimates (90% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. PFS distributions will be summarized using methods developed by Kaplan-Meier.

Time frame
From randomization to progression or death, whichever occurs first, or date of the last computed tomography scan if neither progression nor death has occurred, assessed up to 5 years
3

PFS2

PFS2 may be identified by objective radiological progression using Response Evaluation Criteria in Solid Tumors version (v)1.1., symptomatic deterioration or death. PFS2 will be summarized using treatment hazard ratio estimates (90% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. PFS2 distributions will be summarized using methods developed by Kaplan-Meier.

Time frame
From randomization to objective tumor progression on next-line treatment or death, assessed up to 5 years
4

OS

OS will be summarized using treatment hazard ratio estimates (90% confidence intervals). These estimates will be obtained from outcome-specific Cox-regression models specified with main effects for the randomized treatment and stratified by the factors included in the randomization. OS distributions will be summarized using methods developed by Kaplan-Meier.

Time frame
From randomization to death, assessed up to 5 years

Other outcomes

1

Effect of bevacizumab on PFS

The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). PFS outcome distributions will further be described using methods developed by Kaplan-Meier.

Time frame
Up to 5 years
2

Effect of bevacizumab on OS

The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). OS outcome distributions will further be described using methods developed by Kaplan-Meier.

Time frame
Up to 5 years
3

Effect of bevacizumab on PFS2

The estimates will be obtained from outcome-specific Cox regression models specified with main effects for the assigned treatment arm, physician-choice bevacizumab and the interaction term. The overall effect of bevacizumab will be described by the score test p value for the interaction term. Descriptively, the bevacizumab effect will be summarized using the randomized treatment hazard ratio estimates (95% confidence intervals) within the bevacizumab and no-bevacizumab subgroups (as stratified). PFS2 outcome distributions will further be described using methods developed by Kaplan-Meier.

Time frame
Up to 5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

NRG Oncology

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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